IL-1β, But Not Programed Death-1 and Programed Death Ligand Pathway, Is Critical for the Human Th17 Response to Mycobacterium tuberculosis

Abstract

The programed death-1 (PD-1)-programed death ligand-1 (PD-L1) and PD-L2 co-inhibitory pathway has been implicated in the evasion strategies of <i>Mycobacterium tuberculosis</i>. Specifically, <i>M. tuberculosis</i>-induced PD-L1 orchestrates expansion of regulatory T cells and suppression of Th1 response. However, the role of PD pathway in regulating Th17 response to <i>M. tuberculosis</i> has not been investigated. In the present report, we demonstrate that <i>M. tuberculosis</i> and <i>M. tuberculosis</i>-derived antigen fractions have differential abilities to mediate human monocyte- and dendritic cell (DC)-mediated Th17 response and were independent of expression of PD-L1 or PD-L2 on aforementioned antigen-presenting cells. Importantly, we observed that blockade of PD-L1 or PD-1 did not significantly modify either the frequencies of Th17 cells or the production of IL-17 from CD4⁺ T cells though IFN-γ response was significantly enhanced. On the contrary, IL-1β from monocytes and DCs were critical for the Th17 response to <i>M. tuberculosis</i>. Together, our results indicate that IL-1β, but not members of the programed death pathway, is critical for human Th17 response to <i>M. tuberculosis</i>.